Relative Vaccine Effectiveness of Adjuvanted Trivalent Influenza Vaccine over Three Consecutive Influenza Seasons in the United States

Abstract

Traditional influenza vaccines may be less immunogenic in adults ≥65 years of age due to immunosenescence. Two influenza vaccines-MF59®-adjuvanted trivalent inactivated influenza vaccine (aIIV3) and high-dose influenza vaccine (HD-IIV3)-were developed to overcome this problem. We summarize estimates of the relative vaccine effectiveness (rVE) of aIIV3 vs. HD-IIV3 and aIIV3 vs. standard, egg-based quadrivalent influenza vaccines (IIV4e) during the 2017-2018, 2018-2019, and 2019-2020 US influenza seasons using the same underlying electronic medical record and linked claims dataset for all three seasons. The primary outcome was influenza-related medical encounters (IRMEs), defined by diagnostic codes specific to influenza (ICD J09*-J11*). rVE was estimated using propensity score methods adjusting for demographics and health status. rVE estimates demonstrated consistent benefit for aIIV3 over IIV4e in the overall and at-risk populations. Relative to HD-IIV3, aIIV3 provided improved benefit in the overall study population and comparable benefit in the at-risk population across each season.

Keywords: immunosenescence; influenza; influenza vaccines; relative vaccine effectiveness.

Figure 1

Estimated incidence rates (and 95% uncertainty interval) of influenza-related outcomes (symptomatic illnesses, outpatient visits, hospitalizations, and deaths) per 100,000 individuals ≥65 years of age as estimated by the US Centers for Disease Control and Prevention (CDC) for seasons from 2017–2018, 2018–2019, and 2019–2020 [36,38,39].

Figure 2

Summary of influenza-positive specimens, specified by strain, from individuals ≥65 years of age, as reported by public health laboratories across the United States to the CDC and absolute vaccine effectiveness (aVE) against any strain as estimated by the CDC for individuals ≥65 years of age [26,27,37,40,41,42].

Figure 3

Relative vaccine effectiveness (rVE) of adjuvanted trivalent inactivated influenza vaccine (aIIV3) vs. comparators for the prevention of influenza related medical encounters during the three influenza seasons between 2017 and 2020 in subjects ≥65 years of age and by age subgroups [22,24]. (a) aIIV3 vs. egg-based quadrivalent inactivated influenza vaccine (IIV4e); (b) rVE for aIIV3 vs. high-dose trivalent inactivated influenza vaccine (HD-IIV3). CI, confidence interval.

Figure 4

Relative vaccine effectiveness (rVE) of adjuvanted trivalent inactivated influenza vaccine (aIIV3) vs. comparators during periods of peak influenza activity between 2017 and 2020 in subjects ≥65 years of age and by age subgroups [22,24]. (a) aIIV3 vs. egg-based quadrivalent inactivated influenza vaccine (IIV4e); (b) rVE for aIIV3 vs. high-dose trivalent inactivated influenza vaccine (HD-IIV3). CI, confidence interval.

Figure 4

Relative vaccine effectiveness (rVE) of adjuvanted trivalent inactivated influenza vaccine (aIIV3) vs. comparators during periods of peak influenza activity between 2017 and 2020 in subjects ≥65 years of age and by age subgroups [22,24]. (a) aIIV3 vs. egg-based quadrivalent inactivated influenza vaccine (IIV4e); (b) rVE for aIIV3 vs. high-dose trivalent inactivated influenza vaccine (HD-IIV3). CI, confidence interval.